FUNCtion ALS: Aiming to Restore UNC13A Function in People Living With ALS (FUNCtion ALS)

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 / 2 Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of TRCN-1023 Administered by Intrathecal Injections to Adult People Living With Amyotrophic Lateral Sclerosis

The FUNCtion Amyotrophic Lateral Sclerosis (ALS) trial is a randomized, double-blind, placebo-controlled Phase 1/2 trial to evaluate the safety and tolerability of TRCN-1023 in adults living with ALS. TRCN-1023 is an investigational medicine given as a single injection into the fluid surrounding the spine (intrathecal injection). The trial will also assess how the body processes the drug and whether it shows early signs of benefit over 24 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: TRCN-1023; Other: Placebo

Detailed Description

TRCN-1023 is an investigational medicine designed to restore the function of a protein called UNC13A, which becomes disrupted in most people with Amyotrophic Lateral Sclerosis (ALS) due to a breakdown in how nerve cells process genetic information. This trial is designed to evaluate the safety and tolerability of TRCN-1023 given as a single injection into the fluid surrounding the spine, and to identify the best dose to carry forward into future studies. TRCN-1023 stays in the brain and spinal cord long enough that it may only need to be administered once every 24 weeks. The trial will also assess how the body processes the drug, whether it engages its intended target, and its effects on disease progression, physical function, and quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Adults aged 18 to 75 years
• Diagnosis of ALS (clinically definite, clinically probable, or clinically probable laboratory supported)
• ALS symptoms began within the past 24 months
• Able to perform breathing tests: slow vital capacity (SVC) with consistent results, with breathing capacity of at least 60% of the expected value
• Able and willing to meet all study requirements, including travel to the study site, brain magnetic resonance imaging (MRI) scans, lumbar punctures, and blood draws
• Able and willing to use wearable sensors and complete speech assessments at home
• On a stable dose of approved ALS medication for at least 4 weeks prior to screening
• Capable of providing informed consent

Key Exclusion Criteria:

• Carries a confirmed SOD1 or FUS gene mutation
• Has a tracheostomy or requires continuous assisted ventilation more than 22 hours per day during the preceding 3 months before the first Screening Visit
• Has a contraindication to brain MRI (e.g., pacemaker, metal implants)
• Has a contraindication to lumbar puncture or spinal injection (e.g., blood clotting disorders, certain blood thinners, signs of increased pressure in the brain)
• Has significant abnormal liver, kidney, or blood test results
• Is currently enrolled in another clinical trial or has received an investigational treatment within the past 4 weeks
• Has previously received gene therapy, stem cell therapy, or another Antisense oligonucleotide (ASO) treatment
• Has a clinically significant condition other than ALS that could interfere with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRCN-1023; Antisense oligonucleotide (ASO) administered by intrathecal injection	Drug: TRCN-1023; TRCN-1023 administered as an intrathecal injection.
Placebo Comparator: Placebo; Matching Placebo Comparator	Other: Placebo; Intrathecal injection of artificial cerebrospinal fluid (aCSF).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events	Number and frequency of adverse events assessed over 24 weeks following a single intrathecal injection of TRCN-1023 or placebo	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of TRCN-1023	Plasma TRCN-1023 concentrations	Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24
Cerebrospinal Fluid (CSF) Concentration of TRCN-1023	Cerebrospinal fluid (CSF) TRCN-1023 concentrations	Day 1 (pre-dose and 24 hours post-dose), Weeks 4, 16, and 24 (up to 4 lumbar punctures post-dose)
Time to Peak Plasma Concentration (Tmax)	Time of maximum observed plasma concentration (Tmax) of TRCN-1023	Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24
Peak Plasma Concentration (Cmax) of TRCN-1023	Maximum observed plasma concentration (Cmax) of TRCN-1023	Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24
Area Under the Plasma Concentration-Time Curve to Last Measurable Concentration (AUClast) of TRCN-1023	Area under the plasma concentration-time curve from time zero to last measurable concentration (AUClast) of TRCN-1023	Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24

Collaborators and Investigators

• Sponsor: Trace Neuroscience, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: TRCN-1023-ALS-101; 2025-523111-11 (EudraCT Number); 174619 (Other Identifier: Food And Drug Administration (FDA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No